TY - JOUR
T1 - Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues
AU - Chatterjee, Subroto B.
AU - Dey, Srabani
AU - Shi, Wan Yang
AU - Thomas, Karl
AU - Hutchins, Grover M.
N1 - Funding Information:
This work was supported in part by SCOR P5O-HL-47212-01 and NIH RO1-DK 31722. We thank Dr. Syamal K.Dey (University of Maryland, Baltimore) for developing the computer program that we used for quann'tation of glyco-sphingolipids.
PY - 1997/2
Y1 - 1997/2
N2 - We have measured the levels of glycosphingolipids and the activity of glycosphingolipid glycosyltransferases in human aortic intima and media from patients who died of atherosclerosis. The effects of lactosylceramide (LacCer) and glucosylceramide (GlcCer) from plaque intima on smooth muscle cell proliferation were assessed. When the GlcCer data was expressed as (μg GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-fold increase in plaque intima compared to normal intima was observed. Similarly, the level of LacCer was elevated 5-fold and 4-fold, respectively, compared to unaffected intima. The activity of UDP-GlcCer: ceramide B1 → 4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, B1 → 4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue, LacCer, but not GlcCer derived from plaque intima exerted a ~ 2.8-fold increase in the proliferation of human aortic smooth muscle cells grown in tissue culture compared to control presumably due to a marked increase in LacCer molecular species containing C16:0, C22:1, and C24:0 fatty acids in plaque intima compared to control. In sum, our findings provide an interesting and novel pathogenic mechanism of lactosylceramide mediated plaque formation via stimulation of aortic smooth muscle cell proliferation.
AB - We have measured the levels of glycosphingolipids and the activity of glycosphingolipid glycosyltransferases in human aortic intima and media from patients who died of atherosclerosis. The effects of lactosylceramide (LacCer) and glucosylceramide (GlcCer) from plaque intima on smooth muscle cell proliferation were assessed. When the GlcCer data was expressed as (μg GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-fold increase in plaque intima compared to normal intima was observed. Similarly, the level of LacCer was elevated 5-fold and 4-fold, respectively, compared to unaffected intima. The activity of UDP-GlcCer: ceramide B1 → 4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, B1 → 4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue, LacCer, but not GlcCer derived from plaque intima exerted a ~ 2.8-fold increase in the proliferation of human aortic smooth muscle cells grown in tissue culture compared to control presumably due to a marked increase in LacCer molecular species containing C16:0, C22:1, and C24:0 fatty acids in plaque intima compared to control. In sum, our findings provide an interesting and novel pathogenic mechanism of lactosylceramide mediated plaque formation via stimulation of aortic smooth muscle cell proliferation.
KW - Cell proliferation
KW - GlCer β1 → 4 galactosyltransferase (GalT-2)
KW - Lactosylceramide (LaCer)
KW - Oxidized low density lipoprotein (Ox-LDL)
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U2 - 10.1093/glycob/7.1.57
DO - 10.1093/glycob/7.1.57
M3 - Article
C2 - 9061365
AN - SCOPUS:1842293966
SN - 0959-6658
VL - 7
SP - 57
EP - 65
JO - Glycobiology
JF - Glycobiology
IS - 1
ER -